Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

Objective To explore the brain damage of SD rats under different time points of hypobaric hypoxia exposure.Methods A rat high-altitube cerebral edema(HACE)model was constructed by simulating an altitude of 6 000 m in a hypobaric hypoxia animal experimental chamber.Thirty-six SD male rats were randomly divided into the control group and the hypobaric hypoxia exposure 3,7 and 14 d groups,with 9 rats in each group.Except for the control group,the rats in each group were continuously exposed to hypobaric hypoxia for 3,7,and 14 d.At the end of the modeling period,serum was collected by blood sampling via the abdominal aorta,and brain tissue samples were taken.The wet-to-dry ratio(W/D)of brain tissue was calculated,and the levels of relevant oxidative enzymes in serum and brain tissue were measured.The expression levels of hypoxia-inducible factor-1α(HIF-1α)and aquaporin 4(AQP4)mRNAs in brain tissue were detected by real-time fluorescence quantitative polymerase chain reaction.Results The W/D of brain tissues in the control group and the group exposed to hypobaric hypoxia for 3,7 and 14 d were 4.46±0.12,4.98±0.16,5.07±0.18 and 4.95±0.07;the superoxide dismutase contents were(111.86±2.45),(90.73±1.48),(79.64±2.56)and(55.33±1.45)U·g-1;the glutathione contents were(126.91±5.18),(125.26±1.53),(56.20±2.17)and(122.73±1.78)μg·mL-1;the malondialdehyde contents were(230.94±2.00),(362.65±3.28),(407.34±3.47)and(237.50±1.59)nmol·g-1;the relative expression levels of HIF-1 α mRNA were 1.00±0,2.99±0.49,4.72±0.49 and 1.91±0.28;the relative expression levels of AQP4 mRNA were 1.00±0,2.62±0.34,8.38±0.84 and 5.27±0.42,respectively.Statistically significant differences were found between the above indexes in the 3,7 and 14 d of hypobaric hypoxia exposure group compared with the control group(P＜0.05,P＜0.01).Conclusion Different time of hypobaric hypoxia exposure can up-regulate the expression of AQPs proteins in HACE rats and cause the disruption of the blood-brain barrier,and the HACE model constructed in the hypobaric hypoxia chamber with 6 000 m intervention for 7 d was more stable.

OBJECTIVETo explore the clinical characteristic, therapeutic efficacy and prognosis of patients with hepatitis-associated aplasitc anemia (HAAA).

METHODSthe clinical data and labrotatory examination results of 30 cases of HAAA were analyzed retrospectively, the 6-month response ratio and overall survival (OS) were assessed.

RESULTSHAAA most commonly occured in males, with the occurence rate of males and females was 4:1, the median onset age was 16 (4-43) years old, HAAA oriented focus on sever aplastic anemia (SAA)(4 cases,13%) and very sever aplastic anemia (VSAA)(22 cases,73%). Aplastic anemia (AA) could be seen on occurence of hepatitis (accompanied aplastic anemia) (7 cases,23%), or after the onset of hepatits (delayed aplastic anemia) (23 cases,77%), but more often occured in the latter. Statistical analysis showed that when compared with the patients of delayed aplastic anemia, patients accompanied aplastic anemia possesses lower levels of glutamic-pyruvic transaminase(ALT), aspertate aminotransferase (AST) and total bilirubin (TBIL)(P=0.042,0.012,0.001), and possessed a more obvious lymphoid cell disorder when AA occured, with more lower peripheral blood CD19B cells proportion (P=0.046) and more obvious imbalance of CD4/CD8ratio, but the difference was no statistical significant (P=0538). Factors affecting the 6-month respose were the severity of AA (P=0.044), the peak level of bilirubin of hepatitis (P=0.006) and the propotion of mature monocyte in bone marrow (P=0.034). The long-term follow-up showed that the 2-year OS of HAAA was 64.3±9.2%, the 6-month curative efficacy significantly affect the prognosis (P<0.001).

CONCLUSIONHAAA more often occur in young male, HAAA is mainly SAA and VSAA and mostly non-A-C hepatitis associated aplastic anemia, patients usually have a high incidence of early infection. Patients acompanied with aplastic anemia possess more obvious immunological derangement; the treatment efficacy for HAAA is poor, patients who haven't obtained 6-month response indicate a sinister prognosis, allogeneic hematopoietic stem cell transplantion is a better choice for these patients.

OBJECTIVETo evaluate the efficacy and safety of nateglinide, a new antidiabetic agent, in the treatment of type 2 diabetes.

METHODSA total of 219 treatment-naïve patients with type 2 diabetes from 6 centers were enrolled in this study and blindly divided into nateglinide group (n = 105) and repaglinide group (n = 114). In all patients, the disease was confirmed for at least three months. The whole observation lasted for 12 weeks. The efficacy indicators measured include glycohemoglobin A1c (HbA1c), fasting blood glucose, and 2 hours postprandial blood glucose, and the safety parameters measured included renal and hepatic function, serum lipids, and blood and urea profiles.

RESULTSSimilar decreases in fasting blood glucose, 2 hours postprandial blood glucose, and HbA1 c were found in both nateglinide group and repaglinide group without significant differences. No severe adverse events were noted. The hypoglycemia event reports were not significantly different between these two groups.

CONCLUSIONNateglinide is an effective and safe drug in treating type 2 diabetes.

Blood Glucose ; drug effects ; Cyclohexanes ; administration & dosage ; adverse effects ; therapeutic use ; Diabetes Mellitus, Type 2 ; drug therapy ; Drug Administration Schedule ; Female ; Humans ; Hypoglycemic Agents ; administration & dosage ; adverse effects ; therapeutic use ; Male ; Middle Aged ; Phenylalanine ; administration & dosage ; adverse effects ; analogs & derivatives ; therapeutic use ; Treatment Outcome

Objective To investigate the relationship between cortical watershed infarction and carotid artery stenosis and evaluate the stent insertion operation.Methods After 23 cortical watershed infarction patients diagnosed by CT or MRI received DSA detection,we performed stent insertion operationon 11 patients according to their requirements,and conservative treatment on the remaining 12 patients.All the patients underwent follow up for 6-12 months post-operatively.Results Among the 23 cortical watershed infarction patients,22 Were detected with carotid artery stenosis.Statistical analysis showed that the degree of carotid artery stenosis was associated With the elinical svmDtoms and the volume of steal phenomenon(P<0.05);further,the artery stenosis improvement was over 90%with the stent inserted;conversely,dizziness and steal phenomenon disappeared.The post procedure follow-up,ranging 6-12 months,showed that the patients with stent insertion got less new symptoms,steal phenomenon and artery stenosis,compared with the patients with conservation treatment(P<0.05).Conclusion Cortical watershed infarction is associated with carotid artery stenosis.The stent insertion iS useful for the treatment ofcarotid artery stenosis and prevention of cortical watershed infarction.

Nerve injury produces a long lasting neuropathic pain, manifested as allodynia, a decrease in pain threshold and hyperalgesia, an increase in response to noxious stimuli. The mechanism underlying the lasting abnormal pain is not well understood. Our previous works have shown that electrical tetanic stimulation of the sciatic nerve induces long-term potentiation (LTP) of C-fiber evoked field potentials in the spinal dorsal horn, which is considered as a synaptic model of pathological pain. In the present study we tested if nerve injury, which is proved to produce neuropathic pain, induced the spinal LTP in intact rats. C-fiber evoked field potentials in spinal dorsal horn produced by electrical stimulation (10-20 V, 0.5 ms, 1/min) of the sciatic nerve were recorded. For induction of LTP of C-fiber evoked field potentials, three types of noxious stimuli were applied. (1) Electrical tetanic stimulation (40 V, 0.5 ms pulses at 100 Hz for 1 s repeated four times at 10 s intervals). (2) Transection of the sciatic nerve at 4-5 mm distal to the stimulation electrode. (3) Crushing the sciatic nerve with a forceps four times at 4-5 mm distal to stimulation electrode (from distal to proximal with 1 mm spacing at 10 s intervals), which simulated electrical tetanic stimulation. Acute nerve injury was made by either transection of the sciatic nerve at the distal to the stimulating electrode or crushing the sciatic nerve. We found that nerve injury by cutting or crushing the sciatic nerve produced LTP of C-fiber evoked field potentials lasting until the end of the experiments (3-9 h), and that pretreatment of the sciatic nerve with lidocaine 10 min prior to the nerve transectoin completely blocked LTP induced by nerve transection. The nerve transection-induced LTP was blocked by NMDA receptor antagonist AP5. LTP produced by nerve transection could not be further potentiated by electrical tetanic stimulation, while LTP induced by single electrical tetanic stimulation could be further potentiated by transection of the sciatic nerve. However, when LTP was saturated by several times of electrical tetanic stimulation, nerve transection did not affect the spinal LTP. We conclude that acute nerve injury induces LTP of C-fiber evoked field potentials in intact animals and that nerve transection is more powerful than electrical tetanic stimulation for induction of the spinal LTP. The results further support the notion that LTP of C-fiber evoked field potentials may underlie neuropathic pain.
Animals ; Evoked Potentials ; physiology ; Long-Term Potentiation ; physiology ; Male ; Nerve Fibers, Unmyelinated ; physiology ; Neural Pathways ; drug effects ; physiology ; Nociceptors ; physiology ; Posterior Horn Cells ; enzymology ; physiology ; Rats ; Rats, Sprague-Dawley ; Sciatic Nerve ; injuries ; physiology ; Spinal Cord ; physiology

By using stereological morphometric techniques, we examined the ultrastructure of synapses in lamine II of the spinal dorsal horn of Sprague Dawley rats 30 min, 3 h and 5 h after long-term potentiation (LTP) induction. We found that the numerical density per unit volume (Nv) of total synapses, the thickness of the postsynaptic density (PSD), width of the synaptic cleft increased significantly after the establishment of LTP. (1) Thirty minutes after the formation of LTP, the thickness of the PSD increased from 0.029 +/-0.0064 microm (control) to 0.036 +/-0.009 microm (P<0.05) and the width of the synaptic cleft increased from 0.0181+/-0.0024 microm (control) to 0.0197+/-0.0029 microm (P< 0.05); the number of synaptic vesicles decreased from 0.122 +/-0.011/microm(2) to 0.085 +/-0.010/microm(2) (P<0.05); (2) 3 h after the formation of LTP, the thickness of PSD and the width of the synaptic cleft had no difference compared with those 30 min after LTP. The number of synaptic vesicles increased from 0.122 +/-0.011/microm(2) to 0.138 +/-0.015/microm(2); the curvature of the synaptic interface increased from 1.153+/-0.195 to 1.386 +/-0.311 (P<0.05, compared with control). Nv of negative synapses increased from 0.0187 +/-0.0056 to 0.0543 +/-0.0152 (P<0.05, compared with control), Nv of perforated synapses also increased from 0.0135 +/-0.0053 to 0.0215 +/-0.0076 (P<0.05, compared with control). These data suggest that the increase in thickness of PSD might be the major morphological change during the induction of LTP, while the increase in curvature of the synaptic interface, and the number of perforated synapses might be responsible for the maintenance of the spinal LTP.
Animals ; Long-Term Potentiation ; physiology ; Male ; Posterior Horn Cells ; physiology ; ultrastructure ; Rats ; Spinal Cord ; anatomy & histology ; physiology ; Synapses ; ultrastructure ; Synaptic Transmission ; Synaptic Vesicles ; ultrastructure

Our previous studies have shown that long-term potentiation (LTP) of C-fiber-evoked field potentials in the spinal dorsal horn is NMDA receptor dependent. It is known that elevation of Ca(2+) in the postsynaptic neurons through NMDA receptor channels during high-frequency stimulation of the afferent fibers is crucial for LTP induction, but how this leads to a prolonged potentiation of synaptic transmission in the spinal dorsal horn is not clear. In the hippocampus, a rise of Ca(2+) activates calcium/calmodulin-dependent protein kinase II (CaMK II) through autophosphorylation. Once this occurs, the kinase remains active, even when Ca(2+) concentration returns to baseline level. Phosphorylated CaMK II potentiates synaptic transmission by enhancement of AMPA receptor channel function via phosphorylation of GluR1 subunit of the receptor and the addition of AMPA receptors to synapses. Up to now, the role of CaMK II in the induction and maintenance of LTP of the C-fiber-evoked field potentials in spinal dorsal horn has not been evaluated. In the present study, we examined the expression of CaMK II and phospho-CaMK II in the lumbar segments (L4-L6) of the rat spinal dorsal horn at 30 min and 3 h after the establishment of LTP induced by tetanic electrical stimulation of the sciatic nerve (40 V, 0.5 ms pulses at 100 Hz for 1 s repeated four times at 10 s intervals) by using Western blot and electrophysiological techniques. To determine the role of the phospho-CaMK II in the induction and maintenance of the spinal LTP, a selective CaMK II inhibitor KN-93 (100 micromol/L) was applied directly onto the spinal cord at the recording segments before and after LTP induction. We found that (1) the protein level of phospho-CaMKII increased at both 30 min and 3 h after LTP induction, while the total protein level of CaMK II increased at 3 h but not at 30 min after LTP induction. (2) Spinal application of KN-93 at 30 min prior to the tetanus blocked both LTP induction and the increase in phospho-CaMK II. (3) 30 min after LTP induction, spinal application of KN-93 depressed LTP and the level of phospho-CaMK II (n=3). (4) Spinal application of KN-93 at 3 h after LTP, however, affected neither the amplitude of the spinal LTP nor the level of phospho-CaMK II in the spinal dorsal horn. These results suggest that activation of CaMK II is probably crucial for the induction and the early-phase maintenance of LTP of C-fiber-evoked field potentials in the spinal dorsal horn.
Animals ; Evoked Potentials ; Long-Term Potentiation ; physiology ; Male ; Nerve Fibers, Unmyelinated ; physiology ; Neural Pathways ; drug effects ; physiology ; Phosphoprotein Phosphatases ; metabolism ; Phosphorylation ; Posterior Horn Cells ; enzymology ; physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate ; Spinal Cord ; enzymology ; physiology